Abstract
The goal of this study was to develop a molecular biomarker for the detection of protein aggregation involved in Alzheimer's disease (AD) by exploiting the features of the water saturation transfer spectrum (Z-spectrum), the CEST signal of which is sensitive to the molecular configuration of proteins. A radial-sampling steady-state sequence based ultrashort echo time (UTE) readout was implemented to image the Z-spectrum in the mouse brain, especially the contributions from mobile proteins at the frequency offsets for the composite protein amide proton (+3.6 ppm) and aliphatic proton (−3.6 ppm) signals. Using a relatively weak radiofrequency (RF) saturation amplitude, contributions due to strong magnetization transfer contrast (MTC) from solid-like macromolecules and direct water saturation (DS) were minimized. For practical measure of the changes in the mobile protein configuration, we defined a saturation transfer difference (ΔST) by subtracting the Z-spectral signals at ±3.6 ppm from a control signal at 8 ppm. Phantom studies of glutamate solution, protein (egg white) and hair conditioner show the capability of the proposed scheme to minimize the contributions from amine protons, DS, and MTC, respectively. The ST signal at ±3.6 ppm of the cross-linked bovine serum albumin (BSA) solutions demonstrated that the ΔST signal can be used to monitor the aggregation process of the mobile proteins. High-resolution ΔST images of AD mouse brains at ±3.6 ppm of mouse brains showed significantly reduced ΔST (-3.6) signal compared to the age-matched wild-type (WT) mice. Thus, this signal has potential to serve as a molecular biomarker for monitoring protein aggregation in AD.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 380-390 |
| Number of pages | 11 |
| Journal | NeuroImage |
| Volume | 188 |
| DOIs | |
| State | Published - Mar 1 2019 |
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Keywords
- Alzheimer's disease (AD)
- Chemical exchange saturation transfer (CEST)
- Magnetization transfer contrast (MTC)
- Radial acquisition
- Saturation transfer (ST)
- UTE-CEST
ASJC Scopus subject areas
- Neurology
- Cognitive Neuroscience
Cite this
Protein aggregation linked to Alzheimer's disease revealed by saturation transfer MRI. / Chen, Lin; Wei, Zhiliang; Chan, Kannie W.Y.; Cai, Shuhui; Liu, Guanshu; Lu, Hanzhang; Wong, Philip Chun; Van Zijl, Peter C; Li, Tong; Xu, Jiadi.
In: NeuroImage, Vol. 188, 01.03.2019, p. 380-390.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Protein aggregation linked to Alzheimer's disease revealed by saturation transfer MRI
AU - Chen, Lin
AU - Wei, Zhiliang
AU - Chan, Kannie W.Y.
AU - Cai, Shuhui
AU - Liu, Guanshu
AU - Lu, Hanzhang
AU - Wong, Philip Chun
AU - Van Zijl, Peter C
AU - Li, Tong
AU - Xu, Jiadi
PY - 2019/3/1
Y1 - 2019/3/1
N2 - The goal of this study was to develop a molecular biomarker for the detection of protein aggregation involved in Alzheimer's disease (AD) by exploiting the features of the water saturation transfer spectrum (Z-spectrum), the CEST signal of which is sensitive to the molecular configuration of proteins. A radial-sampling steady-state sequence based ultrashort echo time (UTE) readout was implemented to image the Z-spectrum in the mouse brain, especially the contributions from mobile proteins at the frequency offsets for the composite protein amide proton (+3.6 ppm) and aliphatic proton (−3.6 ppm) signals. Using a relatively weak radiofrequency (RF) saturation amplitude, contributions due to strong magnetization transfer contrast (MTC) from solid-like macromolecules and direct water saturation (DS) were minimized. For practical measure of the changes in the mobile protein configuration, we defined a saturation transfer difference (ΔST) by subtracting the Z-spectral signals at ±3.6 ppm from a control signal at 8 ppm. Phantom studies of glutamate solution, protein (egg white) and hair conditioner show the capability of the proposed scheme to minimize the contributions from amine protons, DS, and MTC, respectively. The ST signal at ±3.6 ppm of the cross-linked bovine serum albumin (BSA) solutions demonstrated that the ΔST signal can be used to monitor the aggregation process of the mobile proteins. High-resolution ΔST images of AD mouse brains at ±3.6 ppm of mouse brains showed significantly reduced ΔST (-3.6) signal compared to the age-matched wild-type (WT) mice. Thus, this signal has potential to serve as a molecular biomarker for monitoring protein aggregation in AD.
AB - The goal of this study was to develop a molecular biomarker for the detection of protein aggregation involved in Alzheimer's disease (AD) by exploiting the features of the water saturation transfer spectrum (Z-spectrum), the CEST signal of which is sensitive to the molecular configuration of proteins. A radial-sampling steady-state sequence based ultrashort echo time (UTE) readout was implemented to image the Z-spectrum in the mouse brain, especially the contributions from mobile proteins at the frequency offsets for the composite protein amide proton (+3.6 ppm) and aliphatic proton (−3.6 ppm) signals. Using a relatively weak radiofrequency (RF) saturation amplitude, contributions due to strong magnetization transfer contrast (MTC) from solid-like macromolecules and direct water saturation (DS) were minimized. For practical measure of the changes in the mobile protein configuration, we defined a saturation transfer difference (ΔST) by subtracting the Z-spectral signals at ±3.6 ppm from a control signal at 8 ppm. Phantom studies of glutamate solution, protein (egg white) and hair conditioner show the capability of the proposed scheme to minimize the contributions from amine protons, DS, and MTC, respectively. The ST signal at ±3.6 ppm of the cross-linked bovine serum albumin (BSA) solutions demonstrated that the ΔST signal can be used to monitor the aggregation process of the mobile proteins. High-resolution ΔST images of AD mouse brains at ±3.6 ppm of mouse brains showed significantly reduced ΔST (-3.6) signal compared to the age-matched wild-type (WT) mice. Thus, this signal has potential to serve as a molecular biomarker for monitoring protein aggregation in AD.
KW - Alzheimer's disease (AD)
KW - Chemical exchange saturation transfer (CEST)
KW - Magnetization transfer contrast (MTC)
KW - Radial acquisition
KW - Saturation transfer (ST)
KW - UTE-CEST
UR - http://www.scopus.com/inward/record.url?scp=85058621057&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058621057&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2018.12.018
DO - 10.1016/j.neuroimage.2018.12.018
M3 - Article
C2 - 30553917
AN - SCOPUS:85058621057
VL - 188
SP - 380
EP - 390
JO - NeuroImage
JF - NeuroImage
SN - 1053-8119
ER -